Title

Phase II Study of the Effects of rhPDGF-BB Injection on Lateral Epicondylitis
A Phase II Randomized, Single Ascending Dose, Double-blinded, Placebo Controlled, Multi-center Study of the Effects of rhPDGF-BB Injection on Lateral Epicondylitis
  • Phase

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    becaplermin ...
  • Study Participants

    100
The purpose of this study is to determine whether recombinant human platelet-derived growth factor (rhPDGF-BB) Injection is effective in the treatment of lateral epicondylitis (tennis elbow).
Methodology: Randomized, single ascending dose, double-blinded, placebo controlled, multi-center study

Study Center(s): 6

Number of Subjects: 100

Diagnosis and Main Inclusion Criteria: Lateral epicondylitis; male and female subjects 21 -80 years of age

Study Drug, Dose, Regimen:

Dose A: sodium acetate buffer alone - placebo control Dose B: sodium acetate buffer + 0.45 mg rhPDGF-BB Dose C: sodium acetate buffer + 0.75 mg rhPDGF-BB Dose D: sodium acetate buffer + 1.5 mg rhPDGF-BB Dose E: sodium acetate buffer + 3.0 mg rhPDGF-BB

Duration and Route of Administration: Single administration dose by injection into the extensor carpi radialis brevis (ECRB)

Duration of Follow-up: 24 weeks (6 months) post-operative follow-up
Study Started
Dec 12
2012
Primary Completion
Oct 21
2014
Study Completion
Oct 21
2014
Results Posted
Jul 02
2019
Last Update
Jul 02
2019

Drug rhPDGF-BB Injection

Comparison of placebo control (0 mg rhPDGF-BB) and different dosages (0.45, 0.75, 1.5, and 3.0 mg) of rhPDGF-BB Injection administered through a one-time injection

Drug Placebo

sodium acetate buffer (0 mg rhPDGF-BB)

Placebo Control Placebo Comparator

Dose A - sodium acetate buffer (0 mg rhPDGF-BB)

0.45 mg rhPDGF-BB Experimental

Dose B - sodium acetate buffer + 0.45 mg rhPDGF-BB

0.75 mg rhPDGF-BB Experimental

Dose C - sodium acetate buffer + 0.75 mg rhPDGF-BB

1.5 mg rhPDGF-BB Experimental

Dose D - sodium acetate buffer + 1.5 mg rhPDGF-BB

3.0 mg rhPDGF-BB Experimental

Dose E - sodium acetate buffer + 3.0 mg rhPDGF-BB

Criteria

Inclusion Criteria:

Subject has signed the Institutional Review Board (IRB) approved Informed Consent Form specific to this study prior to enrollment
Subject has a clinical diagnosis of lateral epicondylitis
Subject's symptoms can be reproduced with resisted supination or wrist dorsiflexion

Subject's symptoms have persisted for at least 3 months despite conservative treatment that includes one or combinations of:

Physical therapy
Splinting
Nonsteroidal antiinflammatory drug (NSAID)
Corticosteroid injection
Subject is independent, ambulatory, and can comply with all post-injection evaluations and visits
Subject is 21-80 years of age and considered to be skeletally mature

Exclusion Criteria:

Subject has undergone previous corticosteroid injection therapy to the effected elbow in less than three months prior to enrollment
Subject has received previous Platelet Rich Plasma (PRP) injection to the affected elbow
Subject is deemed to require a corticosteroid injection into the affected elbow during the course of the study
Subject uses chronic medications known to affect the skeleton (e.g. glucocorticoid usage >10mg/day)
Subject has undergone surgical intervention to the affected elbow for the treatment of lateral epicondylitis

Subject has a positive medical history of any of the following:

medial epicondylitis
radial tunnel syndrome
carpal tunnel syndrome
septic or gouty arthritis
cervical radiculopathy
trauma to the affected elbow within the past 6 weeks
neuromuscular or musculoskeletal deficiency, which limits the ability to perform functional measurement (e.g. grip strength test)
Subject currently has an acute infection at the injection site
Subject has tested positive or been treated for a malignancy in the past or is suspected of having a malignancy or are currently undergoing radio- or chemotherapy treatment for a malignancy anywhere in the body, whether adjacent to or distant from the proposed rhPDGF-BB Injection treatment site
Subject is physically or mentally compromised (e.g. currently being treated for a psychiatric disorder, senile dementia, Alzheimer's disease, etc.) to the extent that the Investigator judges the subject to be unable or unlikely to remain compliant
Subject has an allergy to yeast-derived products
Subject has received an investigational therapy or approved therapy for investigational use within 30 days of injection procedure or during the follow-up phase of this study
Subject is a prisoner, or is known or suspected to be transient
Subject's condition represents a worker's compensation case
Subject is currently involved in a health-related litigation procedure
Subject has documented evidence of a history (e.g. liver testing) of drug/alcohol abuse within the 12 months prior to screening for study entry
Subject is pregnant, or able to become pregnant but not practicing a medically-accepted form of birth control, and/or intending to become pregnant during this study period

Summary

Placebo Control

0.45 mg rhPDGF-BB

0.75 mg rhPDGF-BB

1.5 mg rhPDGF-BB

3.0 mg rhPDGF-BB

All Events

Event Type Organ System Event Term Placebo Control 0.45 mg rhPDGF-BB 0.75 mg rhPDGF-BB 1.5 mg rhPDGF-BB 3.0 mg rhPDGF-BB

Elbow Pain Assessments (VAS), Treated Subjects

Subjects were asked to report current pain level at the fusion site on a 100 mm Visual Analog Scale (with 0 being no pain and 100 being worst pain imaginable).

Placebo Control

Baseline

76.6
score on a scale (Mean)
Standard Deviation: 14.4

Week 12

28.7
score on a scale (Mean)
Standard Deviation: 20.2

Week 2

67.1
score on a scale (Mean)
Standard Deviation: 15

Week 24

16.9
score on a scale (Mean)
Standard Deviation: 21

Week 4

49.9
score on a scale (Mean)
Standard Deviation: 18

Week 8

35.9
score on a scale (Mean)
Standard Deviation: 23.4

0.45 mg rhPDGF-BB

Baseline

77.7
score on a scale (Mean)
Standard Deviation: 9.2

Week 12

31.2
score on a scale (Mean)
Standard Deviation: 21.6

Week 2

73.2
score on a scale (Mean)
Standard Deviation: 14.6

Week 24

23.1
score on a scale (Mean)
Standard Deviation: 25.6

Week 4

49.8
score on a scale (Mean)
Standard Deviation: 21.1

Week 8

39.7
score on a scale (Mean)
Standard Deviation: 19.5

0.75 mg rhPDGF-BB

Baseline

75.9
score on a scale (Mean)
Standard Deviation: 16.9

Week 12

36.7
score on a scale (Mean)
Standard Deviation: 25.3

Week 2

78.5
score on a scale (Mean)
Standard Deviation: 18.4

Week 24

28.5
score on a scale (Mean)
Standard Deviation: 26

Week 4

55.5
score on a scale (Mean)
Standard Deviation: 27

Week 8

47.2
score on a scale (Mean)
Standard Deviation: 20.8

1.5 mg rhPDGF-BB

Baseline

72.0
score on a scale (Mean)
Standard Deviation: 19.9

Week 12

29.8
score on a scale (Mean)
Standard Deviation: 29.7

Week 2

59.7
score on a scale (Mean)
Standard Deviation: 22.7

Week 24

23.8
score on a scale (Mean)
Standard Deviation: 28.2

Week 4

40.2
score on a scale (Mean)
Standard Deviation: 24.1

Week 8

33.0
score on a scale (Mean)
Standard Deviation: 27.2

3.0 mg rhPDGF-BB

Baseline

72.2
score on a scale (Mean)
Standard Deviation: 20.6

Week 12

40.4
score on a scale (Mean)
Standard Deviation: 29

Week 2

70.0
score on a scale (Mean)
Standard Deviation: 26.6

Week 24

32.1
score on a scale (Mean)
Standard Deviation: 31.4

Week 4

52.5
score on a scale (Mean)
Standard Deviation: 27.3

Week 8

39.1
score on a scale (Mean)
Standard Deviation: 28.8

Disabilities of the Arm, Shoulder and Hand (DASH), Treated Subjects

The disabilities of the arm, shoulder and hand (DASH) questionnaire is a self-administered region-specific outcome instrument developed as a measure of self-rated upper-extremity disability and symptoms. The DASH consists mainly of a 30-item disability/symptom scale, scored 0 (no disability) to 100.

Placebo Control

Baseline

43.7
score on a scale (Mean)
Standard Deviation: 13.9

Week 12

12.6
score on a scale (Mean)
Standard Deviation: 8.6

Week 24

7.2
score on a scale (Mean)
Standard Deviation: 9.6

Week 4

29.2
score on a scale (Mean)
Standard Deviation: 12.5

Week 8

21.8
score on a scale (Mean)
Standard Deviation: 11.5

0.45 mg rhPDGF-BB

Baseline

43.5
score on a scale (Mean)
Standard Deviation: 13.5

Week 12

16.7
score on a scale (Mean)
Standard Deviation: 13.2

Week 24

11.4
score on a scale (Mean)
Standard Deviation: 9.9

Week 4

30.9
score on a scale (Mean)
Standard Deviation: 12.8

Week 8

23.0
score on a scale (Mean)
Standard Deviation: 14.2

0.75 mg rhPDGF-BB

Baseline

40.1
score on a scale (Mean)
Standard Deviation: 19.8

Week 12

19.8
score on a scale (Mean)
Standard Deviation: 15.3

Week 24

14.5
score on a scale (Mean)
Standard Deviation: 17.3

Week 4

34.1
score on a scale (Mean)
Standard Deviation: 18.3

Week 8

24.7
score on a scale (Mean)
Standard Deviation: 14.9

1.5 mg rhPDGF-BB

Baseline

40.0
score on a scale (Mean)
Standard Deviation: 15.3

Week 12

16.1
score on a scale (Mean)
Standard Deviation: 15.9

Week 24

13.8
score on a scale (Mean)
Standard Deviation: 15.6

Week 4

27.8
score on a scale (Mean)
Standard Deviation: 20.2

Week 8

19.7
score on a scale (Mean)
Standard Deviation: 16.4

3.0 mg rhPDGF-BB

Baseline

41.3
score on a scale (Mean)
Standard Deviation: 18.5

Week 12

24.5
score on a scale (Mean)
Standard Deviation: 23.7

Week 24

19.6
score on a scale (Mean)
Standard Deviation: 24.3

Week 4

38.3
score on a scale (Mean)
Standard Deviation: 22.9

Week 8

25.1
score on a scale (Mean)
Standard Deviation: 22.5

Total Score Patient Rated Tennis Elbow Evaluation (PRTEE), All Treated Subjects

The Pain and disability measured by the Patient Rated Tennis Elbow Evaluation (PRTEE) is a 15-item questionnaire designed to measure forearm pain and disability in patients with lateral epicondylitis (also known as "tennis elbow"). The PRTEE allows patients to rate their levels of tennis elbow pain and disability from 0 to 10, and consists of 2 subscales: PAIN subscale (0 = no pain, 10 = worst imaginable) -Pain - 5 items FUNCTION subscale (0 = no difficulty, 10 = unable to do) Specific activities - 6 items Usual activities - 4 items In addition to the individual subscale scores, a total score can be computed on a scale of 100 (0 = no disability), where pain and functional problems are weighted equally

Placebo Control

Baseline

52.6
score on a scale (Mean)
Standard Deviation: 17.9

Week 12

13.5
score on a scale (Mean)
Standard Deviation: 8

Week 24

7.8
score on a scale (Mean)
Standard Deviation: 10

Week 4

34.7
score on a scale (Mean)
Standard Deviation: 14.5

Week 8

25.2
score on a scale (Mean)
Standard Deviation: 15.2

0.45 mg rhPDGF-BB

Baseline

56.0
score on a scale (Mean)
Standard Deviation: 14.3

Week 12

18.2
score on a scale (Mean)
Standard Deviation: 16.4

Week 24

12.1
score on a scale (Mean)
Standard Deviation: 12.4

Week 4

39.2
score on a scale (Mean)
Standard Deviation: 15.3

Week 8

26.9
score on a scale (Mean)
Standard Deviation: 17.4

0.75 mg rhPDGF-BB

Baseline

48.3
score on a scale (Mean)
Standard Deviation: 16.3

Week 12

22.3
score on a scale (Mean)
Standard Deviation: 16.4

Week 24

16.2
score on a scale (Mean)
Standard Deviation: 17.9

Week 4

39.3
score on a scale (Mean)
Standard Deviation: 21.7

Week 8

28.9
score on a scale (Mean)
Standard Deviation: 15.1

1.5 mg rhPDGF-BB

Baseline

52.6
score on a scale (Mean)
Standard Deviation: 20.7

Week 12

20.1
score on a scale (Mean)
Standard Deviation: 22.7

Week 24

16.8
score on a scale (Mean)
Standard Deviation: 19.3

Week 4

32.2
score on a scale (Mean)
Standard Deviation: 23.9

Week 8

25.4
score on a scale (Mean)
Standard Deviation: 21

3.0 mg rhPDGF-BB

Baseline

52.3
score on a scale (Mean)
Standard Deviation: 22.9

Week 12

26.8
score on a scale (Mean)
Standard Deviation: 24.8

Week 24

22.3
score on a scale (Mean)
Standard Deviation: 27.3

Week 4

43.4
score on a scale (Mean)
Standard Deviation: 24.3

Week 8

28.6
score on a scale (Mean)
Standard Deviation: 24.9

Grip Strength Test, All Treated Subjects

Grip strength testing will be performed to evaluate changes in the strength and sincerity of effort as a result of treatment for lateral epicondylitis. Testing will be performed to assess the pain-free grip strength (performing the test until discomfort is felt) and maximum grip strength (performing the test to the maximum of their ability). The test will be performed while the patient is standing with the elbow in full extension, as this position has been used to assess grip strength in patients with lateral epicondylitis. A Jamar Plus+ Digital Hand Dynamometer with the grip in the second position will be used because the second position has been assumed to be the most reliable and consistent position. Patients will be asked to perform three repetitions of each test (pain-free and maximum) at each study interval and the mean score will be calculated and used for analysis.

Placebo Control

Baseline

42.6
lbs. (Mean)
Standard Deviation: 30.1

Week 12

58.2
lbs. (Mean)
Standard Deviation: 28.1

Week 24

66.4
lbs. (Mean)
Standard Deviation: 26.4

Week 4

40.2
lbs. (Mean)
Standard Deviation: 25.6

Week 8

53.5
lbs. (Mean)
Standard Deviation: 27.8

0.45 mg rhPDGF-BB

Baseline

33.4
lbs. (Mean)
Standard Deviation: 24.1

Week 12

61.0
lbs. (Mean)
Standard Deviation: 37.7

Week 24

69.1
lbs. (Mean)
Standard Deviation: 37.5

Week 4

44.5
lbs. (Mean)
Standard Deviation: 32

Week 8

50.6
lbs. (Mean)
Standard Deviation: 36.3

0.75 mg rhPDGF-BB

Baseline

47.6
lbs. (Mean)
Standard Deviation: 29.4

Week 12

67.5
lbs. (Mean)
Standard Deviation: 38.3

Week 24

79.9
lbs. (Mean)
Standard Deviation: 33.4

Week 4

48.3
lbs. (Mean)
Standard Deviation: 33

Week 8

64.6
lbs. (Mean)
Standard Deviation: 35

1.5 mg rhPDGF-BB

Baseline

39.6
lbs. (Mean)
Standard Deviation: 28.9

Week 12

61.1
lbs. (Mean)
Standard Deviation: 32.1

Week 24

69.9
lbs. (Mean)
Standard Deviation: 29.1

Week 4

52.0
lbs. (Mean)
Standard Deviation: 30.2

Week 8

53.3
lbs. (Mean)
Standard Deviation: 29

3.0 mg rhPDGF-BB

Baseline

39.7
lbs. (Mean)
Standard Deviation: 23.2

Week 12

45.1
lbs. (Mean)
Standard Deviation: 25.3

Week 24

62.9
lbs. (Mean)
Standard Deviation: 25.7

Week 4

41.9
lbs. (Mean)
Standard Deviation: 26.3

Week 8

54.8
lbs. (Mean)
Standard Deviation: 26.4

Maximum Grip Strength, Treated Subjects

A higher grip strength score indicates an improvement. A positive change from baseline indicates an improvement. Grip strength testing will be performed to evaluate changes in the strength and sincerity of effort as a result of treatment for lateral epicondylitis. Testing will be performed to assess the pain-free grip strength (performing the test until discomfort is felt) and maximum grip strength (performing the test to the maximum of their ability). The test will be performed while the patient is standing with the elbow in full extension, as this position has been used to assess grip strength in patients with lateral epicondylitis. A Jamar Plus+ Digital Hand Dynamometer with the grip in the second position will be used because the second position has been assumed to be the most reliable and consistent position. Patients will be asked to perform three repetitions of each test (pain-free and maximum) at each study interval and the mean score will be calculated and used for analysis.

Placebo Control

Baseline

60.4
lbs. (Mean)
Standard Deviation: 35

Week 12

78.9
lbs. (Mean)
Standard Deviation: 29.9

Week 24

82.5
lbs. (Mean)
Standard Deviation: 32.7

Week 4

62.9
lbs. (Mean)
Standard Deviation: 26.2

Week 8

73.3
lbs. (Mean)
Standard Deviation: 29.3

0.45 mg rhPDGF-BB

Baseline

58.7
lbs. (Mean)
Standard Deviation: 33.1

Week 12

68.6
lbs. (Mean)
Standard Deviation: 31.2

Week 24

71.0
lbs. (Mean)
Standard Deviation: 32.5

Week 4

63.5
lbs. (Mean)
Standard Deviation: 33.1

Week 8

66.4
lbs. (Mean)
Standard Deviation: 31.3

0.75 mg rhPDGF-BB

Baseline

71.8
lbs. (Mean)
Standard Deviation: 38.9

Week 12

81.8
lbs. (Mean)
Standard Deviation: 39.7

Week 24

80.7
lbs. (Mean)
Standard Deviation: 33.7

Week 4

64.2
lbs. (Mean)
Standard Deviation: 37.2

Week 8

72.9
lbs. (Mean)
Standard Deviation: 37

1.5 mg rhPDGF-BB

Baseline

60.3
lbs. (Mean)
Standard Deviation: 31.2

Week 12

74.5
lbs. (Mean)
Standard Deviation: 32.8

Week 24

77.8
lbs. (Mean)
Standard Deviation: 27

Week 4

68.9
lbs. (Mean)
Standard Deviation: 35.5

Week 8

71.6
lbs. (Mean)
Standard Deviation: 30

3.0 mg rhPDGF-BB

Baseline

61.3
lbs. (Mean)
Standard Deviation: 29.7

Week 12

65.1
lbs. (Mean)
Standard Deviation: 30

Week 24

76.4
lbs. (Mean)
Standard Deviation: 30.9

Week 4

62.0
lbs. (Mean)
Standard Deviation: 33

Week 8

66.9
lbs. (Mean)
Standard Deviation: 31.5

Total

100
Participants

Age, Customized

Race (NIH/OMB)

Sex: Female, Male

Overall Study

Placebo Control

0.45 mg rhPDGF-BB

0.75 mg rhPDGF-BB

1.5 mg rhPDGF-BB

3.0 mg rhPDGF-BB